Heavy alcohol use is common and presents a major social/economic challenge. Although chronic use of small amounts of alcohol is not always harmful, heavier use (>2 drinks/day) is generally harmful and frequently leads to alcoholism-the most common forms being alcohol abuse (AA) and alcohol dependence (AD). AA/AD affect ~25% of the U.S. population and cause nearly $200 billion/yr of economic damage and untold human misery. These adverse outcomes are potentially avoidable if the alcohol abuse is spotted early; however, current screening methods for chronic alcohol use capture alcohol usage only in the hours prior to testing or rely on insensitive, non-specific protein assays. A next-generation method that could more reliably identify chronic alcohol abuse and monitor abstinence would be of great interest to a large number of groups, including medical, governmental, security and transportation agencies. Developing, validating, and commercializing such a next-generation technology is Behavioral Diagnostic's overall goal. In this Phase I feasibility study, we will build upon our extensive experience in substance use epigenetics and will seek to achieve two goals. First, we will unequivocally demonstrate that the overall patterns of methylation associated with alcohol use are reliable. Second, we will determine the stability of DNA methylation in the absence of immediate alcohol use. In this Phase I project, we propose to do this by first validating the results from a prior genome-wide analysis of alcohol associated DNA methylation changes by comparing the methylation profiles of abstinent controls with that of heavy drinkers admitted for acute detoxication. We will then follow these drinkers through a 30 day inpatient treatment stay and check methylation at the most significantly differentially methylated residues after 30 days of inpatient assured abstinence to determine which are stable (trait marker) and which start the process of reverting to the population mean (state marker and possible indicator of treatment associated abstinence). If successful, this project will be a significant advancement for the field and will serve as proof of principle for our Phase II development of a full-scale diagnostic tool for both the detection and quantitation of chronic alcohol use and monitor abstinence in patients after discharge. This highly innovative proposal is significant because the development of easy to use, relatively foolproof diagnostic tests for these disorders could find widespread acceptance in medical, civil and forensic applications. The company is well prepared to conduct the studies for several reasons. First, Dr. Philibert, is a co-inventor of the technology, is a board certified psychiatrist with extensive experience in all aspects of the proposed studies , and has direct capability of overseeing any potential Phase II of this study. Second, Dr. Osborn, the CEO, has thirty years of experience in bio-industry and is well connected to the biomedical and bioventure communities. Fourth, we are further aided by a team of ethicists and substance use specialists. Fourth, the company has secured intellectual properties rights with respect to this and other related technologies.